Diversity in EWAS: current state, challenges, and solutions
AbstractHere, we report a lack of diversity in epigenome-wide association studies (EWAS) and DNA methylation (DNAm) data, discuss current challenges, and propose solutions for EWAS and DNAm research in diverse populations. The strategies we propose include fostering community involvement, new data generation, and cost-effective approaches such as locus-specific analysis and ancestry variable region analysis. (Source: Genome Medicine)
Source: Genome Medicine - July 6, 2022 Category: Genetics & Stem Cells Source Type: research
Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations
ConclusionsBy integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare. (Source: Genome Medicine)
Source: Genome Medicine - June 29, 2022 Category: Genetics & Stem Cells Source Type: research
Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes
ConclusionsWe conclude thatSORL1-LoF variants should be interpreted in light ofAPOE genotypes for future clinical applications. (Source: Genome Medicine)
Source: Genome Medicine - June 28, 2022 Category: Genetics & Stem Cells Source Type: research
An introduction to spatial transcriptomics for biomedical research
AbstractSingle-cell transcriptomics (scRNA-seq) has become essential for biomedical research over the past decade, particularly in developmental biology, cancer, immunology, and neuroscience. Most commercially available scRNA-seq protocols require cells to be recovered intact and viable from tissue. This has precluded many cell types from study and largely destroys the spatial context that could otherwise inform analyses of cell identity and function. An increasing number of commercially available platforms now facilitate spatially resolved, high-dimensional assessment of gene transcription, known as ‘spatial transcripto...
Source: Genome Medicine - June 27, 2022 Category: Genetics & Stem Cells Source Type: research
Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease
ConclusionsAbnormal histone hyperacetylation facilitates DNA damage in steatotic hepatocytes and is a potential initiating event in hepatocellular carcinogenesis. (Source: Genome Medicine)
Source: Genome Medicine - June 23, 2022 Category: Genetics & Stem Cells Source Type: research
Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications
ConclusionsWe find that upon re-evaluation of undiagnosed patients, both reanalysis of existing ES data as well as resequencing strategies are needed to identify additional genetic diagnoses. Importantly, not all patients are routinely re-evaluated in clinical care, prolonging their diagnostic trajectory, unless systematic reanalysis is facilitated. We have translated our observations into considerations for systematic and ad hoc reanalysis in routine genetic care. (Source: Genome Medicine)
Source: Genome Medicine - June 17, 2022 Category: Genetics & Stem Cells Source Type: research
Integrated genomic analyses of acral and mucosal melanomas nominate novel driver genes
ConclusionsOur meta-analysis expands the catalog of driver mutations in acral and mucosal melanomas, sheds new light on their pathogenesis and broadens the catalog of therapeutic targets for these difficult-to-treat cancers. (Source: Genome Medicine)
Source: Genome Medicine - June 16, 2022 Category: Genetics & Stem Cells Source Type: research
Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women
ConclusionsThese data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers.Trial registrationClinical trial 1Mifepristone treatment prior to insertion of a levonorgestrel releasing intrauterine system for improved bleeding control – a randomized controlled trial, clinicaltrialsregister.eu,2009-009014-40; registered on 20 July 2009.Clinical trial 2The effect of a progesterone receptor modulator on breast tissue in women with BRCA1 and 2 mutations, clinicaltrials.gov,NCT01898312; registered on 07 May 2013.Clinical trial 3A pilot prevention study of the effects of the anti- ...
Source: Genome Medicine - June 15, 2022 Category: Genetics & Stem Cells Source Type: research
Mendelian randomization analysis of 37 clinical factors and coronary artery disease in East Asian and European populations
ConclusionsWe confirmed the causal effects of 10 cardiometabolic traits on CAD and identified causal risk effects of RBC, hemoglobin, hematocrit, and UA independent of traditional cardiometabolic factors. We found no causal effects for 23 clinical factors, despite their reported epidemiological associations. Our findings suggest the physiology of red blood cells and the level of UA as potential intervention targets for the prevention of CAD. (Source: Genome Medicine)
Source: Genome Medicine - June 14, 2022 Category: Genetics & Stem Cells Source Type: research
Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome
ConclusionsThis study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences ofKCNK9 variation on channel function and regulation. (Source: Genome Medicine)
Source: Genome Medicine - June 13, 2022 Category: Genetics & Stem Cells Source Type: research
Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history
ConclusionsThese results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population. (Source: Genome Medicine)
Source: Genome Medicine - June 10, 2022 Category: Genetics & Stem Cells Source Type: research
Addressing the routine failure to clinically identify monogenic cases of common disease
This article seeks to focus attention on the need for universal genetic testing in common diseases for which the recommended clinical management of patients with specific monogenic forms of disease diverges from standard management and has evidence for improved outcomes.We review evidence from genomic screening of large patient cohorts, which has confirmed that important monogenic case identification failures are commonplace in routine clinical care. These case identification failures constitutediagnostic misattributions, where the care of individuals with monogenic disease defaults to the treatment plan offered to those w...
Source: Genome Medicine - June 7, 2022 Category: Genetics & Stem Cells Source Type: research
Combined exome and transcriptome sequencing of non-muscle-invasive bladder cancer: associations between genomic changes, expression subtypes, and clinical outcomes
ConclusionsMulti-omic data may facilitate better prognostication and selection of therapeutic interventions in patients with G3pT1 NMIBC. These findings demonstrate the potential for improving the management of high-risk NMIBC patients and warrant further prospective validation. (Source: Genome Medicine)
Source: Genome Medicine - June 3, 2022 Category: Genetics & Stem Cells Source Type: research
Comprehensive genomic and tumour immune profiling reveals potential therapeutic targets in malignant pleural mesothelioma
ConclusionsWe propose accounting for genomic and immune microenvironment status may influence therapeutic planning in the future. (Source: Genome Medicine)
Source: Genome Medicine - May 30, 2022 Category: Genetics & Stem Cells Source Type: research
Transcriptomic perspectives of memory-like NK cells and aging
AbstractA recent study highlights the presence of a unique memory-like natural killer (NK) cell subset, which accumulates with aging and appears to associate withdisease severity in COVID-19 patients. While the clinical relevance of memory in NK cells is being debated, the molecular identity of this subset in the form of a single-cell transcriptome is essential to define their origin, longevity, functions, and disease relevance. (Source: Genome Medicine)
Source: Genome Medicine - May 25, 2022 Category: Genetics & Stem Cells Source Type: research
